Combined electric and magnetic field therapy for bone repair and regeneration: an investigation in a 3-mm and an augmented 17-mm tibia osteotomy model in sheep

Background Therapies using electromagnetic field technology show evidence of enhanced bone regeneration at the fracture site, potentially preventing delayed or nonunions. Methods Combined electric and magnetic field (CEMF) treatment was evaluated in two standardized sheep tibia osteotomy models: a 3-mm non-critical size gap model and a 17-mm critical size defect model augmented with autologous bone grafts, both stabilized with locking compression plates. CEMF treatment was delivered across the fracture gap twice daily for 90 min, starting 4 days postoperatively (post-OP) until sacrifice (9 or 12 weeks post-OP, respectively). Control groups received no CEMF treatment. Bone healing was evaluated radiographically, morphometrically (micro-CT), biomechanically and histologically. Results In the 3-mm gap model, the CEMF group (n = 6) exhibited higher callus mineral density compared to the Control group (n = 6), two-fold higher biomechanical torsional rigidity and a histologically more advanced callus maturity (no statistically significant differences). In the 17-mm graft model, differences between the Control (n = 6) and CEMF group (n = 6) were more pronounced. The CEMF group showed a radiologically more advanced callus, a higher callus volume (p = 0.003) and a 2.6 × higher biomechanical torsional rigidity (p = 0.024), combined with a histologically more advanced callus maturity and healing. Conclusions This study showed that CEMF therapy notably enhanced bone healing resulting in better new bone structure, callus morphology and superior biomechanical properties. This technology could transform a standard inert orthopedic implant into an active device stimulating bone tissue for accelerated healing and regeneration. Supplementary Information The online version contains supplementary material available at 10.1186/s13018-023-03910-6.


Table of Content Page
Animal 86.01 (CEMF group, 3mm gap model) had to be excluded from the group analysis due to implant failure of the internal fixation. A complete collapse of the fracture gap laterally at the trans cortex was already detected 3 weeks post-surgery during radiographic examination. The two most distal screws (hole 11 and 12) were broken and the screw in hole 9 (closest to the distal end of the defect) was displaced and bent). The sheep showed a very nervous, anxious and uncooperative behavior jumping a lot trying to escape. This was likely the primary cause of the fixation failure.
In animal 86.02 (CEMF group, 3mm gap model) the macroscopic evaluation at sacrifice at 9 weeks post-OP revealed a moderately detached transducer cap at the proximal Marvel screw with fibrous tissue between cap and screw head. As it was not detected with radiographic follow up, the exact time point of cap detachment could not be determined. Therefore, the CEMF treatment may not have been systematically administered throughout the in-life phase. This observation prompted the decision to exclude this animal from the analysis.

Clinical findings and complications
In the 3mm gap model, in one sheep (86.10, CEMF group), the postoperative radiograph revealed a detached cap at the distal CEMF screw. This sheep, still under anesthesia, underwent a second surgery and the cap was fixed at the screw head again. Even though the anesthesia time was prolonged, no complications occurred during anesthesia nor postoperatively. Cap detachment was also detected radiographically 3 -7 weeks post-surgery in 3 Control group sheep (86.04, 86.07, 86.08), but no reattachment was attempted as all 3 sheep were not receiving CEMF treatment. The proximal CEMF screw cap loosening in sheep 86.12 (CEMF group) was detected 5 weeks post-surgery. In this case, a second surgery was performed the same day to reattach the cap (5 cm long incision above proximal CEMF screw). Antibiotics (penicillin, gentamycin) and analgesics (Carprofen) were given intravenously for three days. No further complications evolved from this event and therefore this animal was included in the group analysis.
An anesthesia complication occurred with sheep 86.07 (control group). The animal developed a respiratory arrest immediately after extubation followed by pulmonary edema, which was immediately treated with furosemide. No further complications occurred during the recovery period and the in-life phase of this sheep. While appropriate actions were immediately taken to ensure survival of the sheep, return to full consciousness, sufficient spontaneous respiration and a stable circulatory function was achieved only within an hour.
The hypoxia and hypoperfusion of the region of interest during this time could have likely compromised the vitality and initial recruitment of cells needed during the early phase of bone healing. It is speculated that, from this complication, even later healing phases were affected. Indeed, at sacrifice, the fracture ends were movable and the gap unstable.          Negative control group sheep (17 mm non-augmented defect) Three sheep were operated as part of a negative control group. In this case, the tibia defect created was 17mm long and was not augmented with autologous bone. CEMF devices were implanted as with other CEMF or control animals, but CEMF treatment was not applied, as with Control group animals. All three sheep showed non-healed defects at 12-weeks post-operatively, as seen in the radiographs below. This finding showed that a non-augmented 17mm gap tibia defect would not spontaneously heal in this model.